Unit 2: Lipids

lipids

• have low solubility in water

• high solubility in np solvents

• mostly hydrocarbons

membrane lipids are

amphipathic

types of lipids

what percent of calories should come from fat

20-35%

healthy aspects of fat in diet

• promote satiety

• carry fat-soluble vitamins (like coenzymes)

• major source of fatty acids (omega 3 and omega 6)

• important precursors to eicosanoids (signaling molecules)

lipids are very

diverse molcules

cells use __% of their genes to synthesize lipids

5%

ubiquinone

lipid important for shuttling in the ETC

sterols

hormones used in cell signaling

lipids are classified by

function

• storage

• membrane

• signaling

• coenzymes

• pigments

• antioxidants

every lipid type

• triacylglycerols

• waxes

• phospholipids

• sphingolipids

• glycolipids

• eicosanoids

• steroids

• lipoproteins

• fat-souble vitamins

• glycerophsopholipids

• sphinegomyelins

• cerebrosides

• gangliosides

• prostaglandins

• thromboxanes

• leokotrienes

which lipid is the simplest?

fatty acids

fatty acids

• are often constituents of more complex lipids

• made up of a long hydrocarbon tail and a carboxyl head group

• usually have an even number of carbons (12-24)

• most are unbranched

• C1 is the carbon by the carboxylic head

saturated fatty acids

• straight, not kinked

• have as many hydrogens bound to the tail as possible, since no C=C bonds

unsaturated fatty acids

• kinked due to C=C bonds, which also causes it to have fewer hydrogens, so “unsaturated”

• monosaturated has one C=C bond in the chain, polyunsaturated has more than one double bond

• double bonds are usually at positions C9,12,15

carboxylic acids have highly reduced _____

hydrocarbon chains (4-36 carbons)

fatty acid naming

#carbons: #double bonds (Δ^#carbon where double bond starts)

saturated fatty acid chains can adopt

extended conformations

______ fatty acids are more abundant in nature than _____

unsaturated are more abundant than saturated

double bonds in  natural unsaturated fatty acids are typically in _____ conformation

cis

• this causes the chain to kink and incr flexibility since it prevents close packing

more solid fats have a greater proportion of saturated fats due to ____

VDWs forces being higher in more solid fats

fatty acids rarely occur in a _____ state

free, uncomplexed

how do free fatty acids circulate the body of vertebrates?

they bind to a protein carrier called serum albumin

fatty acids are typically present as _______ derivatives

carboxylic acid

• often esterified to glycerol (to form triglycerides) or other backbone structures

• fatty acids like to bind to something

triglycerides are aka

fats, and TAGs

• fatty acid esters of glycerol

• have 3 fatty acids each ester linked to a single glycerol molecule

• serves as a major energy source for organisms

• humans store energy as there fats for up to weeks

• TAGs are the most reduced form of carbon in nature, so it has super high PE due to so many np bonds, and good for energy storage

adipose tissue

forms because fats are hydrophobic and want to aggregate in the aqueous body

TAGs are used for ____ in many animals

insulation and energy source

• sperm whales use it in their head to be able to dive deep down

• people used to hunt their heads for fuel since it has so much oil /fat in there

wax

• used for storage and as a water repellent

• formed form esters of long chain saturated (C14-36) and unsaturated with long-chain alcohols (C16-30)

• used to protect hair, skin, makes up beeswax to be water repellent, birds cover their wings in it to repel water, etc

polar lipids in membranes

have a polar head group and np tail (uaully attached to fatty acids)

• differ in their backbones, fatty acids, and head groups

each side of a lipid bilayer is called a

leaflet

membrane lipids

• are amphipathic

• form bilayers

• one layer faces cytoplasm and the other faces ECM

• for membranes of organelles, one side faces cytosol and the other faces organelle lumen

• bilayers are 4-5nm think

phospholipids

have a hydrophobic region attached to a phosphate, attached to a polar head group

glycolipids

have a hydrophobic region attached to a polar head group that is a sugar

sterols

four fused hydrocarbon rings

• rigid

if a phospholipid has a ____ backbone, it is a ____

if glycerol backbone, glycerophospholipid

• has 2 fatty acids at C1 and C2 (usually one is saturated and one is not) each is connected to an OH on the glycerol to form ester linkages

• C3 has the polar or charged head group that is attached to the backbone by a phosphate

if sphingosine backbone, phosphosphingolipid

• has only one fatty acid at C2 (since sphingosine already has/is a hydrocarbon chain on it)

  • the fatty acids connects to the backbone via an amide linkage

• has its polar head group at C1

glycerophospholipid

• has 2 fatty acids at C1 and C2 (usually one is saturated and one is not) each is connected to an OH on the glycerol to form ester linkages

• C3 has the polar or charged head group that is attached to the backbone by a phosphate

phosphosphingolipid

• has only one fatty acid at C2 (since sphingosine already has/is a hydrocarbon chain on it)

  • the fatty acids connects to the backbone via an amide linkage

• has its polar head group at C1

glycerophospholipid polar head groups

• polar groups are esterified to the backbone

• phosphatidic acid: lacks a head group (is parent coumpound)

• phosphatidylethanolamine: has ethanolamine has head group (ethyl connected to an amine)

• phosphatidylcholine: has choline (N(CH3)3 head group

• phosphatidylserine: has serine head group 

• posphatidyglycerol: has glycerol as head group

• phosphatidylionsitol: has 6 carbon sugar ring as head group

parent compound of glycerophospholipids

phosphatidic acid (lacks the polar head group)

phosphatidylethanolamine head group

phosphatidylcholine head group

phosphatidylserine head group

phosphatidyglycerol head group

phosphatidylionsitol head group

6 carbon sugar ring structure

parent compound of sphingolipids

ceramide (which is sphingosine with a fatty acid)

diff types of sphingilipids

• ceramide is parent compound

• sphingomyelin

• glucosylceramide

• lactosylceramide

• ganglioside

sphingomyelin

sphingolipid with a phosphocholine head group

glucosylceramide

sphingolipid with glucose head group

lactosylceramide

sphingolipid with di, tri, or tetrasaccharide head group

ganglioside

sphingolipid with complex oligosaccharide head group

sphingolipids are under the glycolipid subcategory if they have

sugars but no phosphate attached

3 subclasses of sphingolipids

• sphingomyelins

  • have phosphate attached to a choline as head group

• cerebrosides

  • have one sugar as head group and are glycolipids since no phosphate

• gangliosides

  • have multiple sugars attached but no phosphates, so is a glycolipid

• cerebrosides and gangliosides are both classified as glycosphingolipids and are in the brain/nervous system

  • ex: sphingomyelines form the myelin sheath to insulate neurons

there are many types of sphingolipids

can have one or more sugars attached

• each has their polar head group attached to the C3 1-hydroxyl of their sphingosine

gangliosides

• a complex glycosphingolipid

• have a ceramide backbone with two or more esterified sugars attached, one of which must be sialic acid

• functions in cell-to-cell recognition, tissue immunity, nerve impulse transmission, GM2 builds up in people with Tay-Sachs disease

phospholipids and sphingolipids can be degraded by

lipases

• enzymes in lysosomes

• each hydrolyzable bond in the lipid has its own enzyme that can degrade it, see example on slide how one enzyme removes the head group, one the fatty acid number one, etc

• enzymes remove each sugar in a stepwise fashion

defects in lipid homeostasis can lead to

several disease

• lysosomal storage diseases

lysosomal storage diseases

• a genetic affect that causes accumulation of lipids in cells when gangliosides are not being degraded by lysosomal enzymes properly

• this prevents the lysosome from doing its normal function and can be deadly

• you need an enzyme to break down each type of sugar in the lipid

isoprene

5 carbon unit

• isoprenoids are steroids made up of isoprenes

isoprenoids

steroids made up of isoprenes

ex of steroid hormones

testosterone

estradiol

cortisol

5 lipid vitamins

A, D, E, K, Q

sterols

subcategory of steroids

terpenes

a diverse group of molecules often recognized by their characteristic flavors, colors, odors

3 types of Eicosanoids

• prostaglandins

• thromboxanes

  • leokotrienes

most bacteria cannot synthesize

sterols

• but most eukaryotes can

sterol structure

• four fused carbon rings that is almost planar forms the main section

• has a hydroxyl polar head group off of one ring

• has various side chains

• see image of cholesterol

all steroid hormones are derived from

cholesterol

sterols (like cholesterol) affect

membrane fluidity

if there are more sterols between unsaturated fatty acid chains in a membrane, fluidity of the membrane

decr, since the sterols incr the VDWs forces of the unsaturated fatty acids

if there are more sterols between saturated fatty acid chains in a membrane, fluidity of the membrane

incr, since sterols disrupt the VDWs between saturated fatty acid chains

_____ are isoprene/terpene based lipids

steroid hormones

steroid hormones

• oxidized derivatives of sterols

• have sterol structure but with shorter/no side chains and more oxygens bound

• steroid hormones are signalers that travel through the blood on protein carriers. They bind to nuclear receptors of trigger gene expression changes

terpenes

• have multiple isoprene structures, each of 5 carbon units, but have conjugated double bonds, which absorb visible light

• so multiple isoprenes with conjugated pi bonds together in a single molecule

• recognized for their odor/bright color/flavor (pigments)

more isoprenes in a molecule means the ____ is longer

terpene

vitamin A

• aka retinol

• is a terpene

• 20 carbon hormone

• its predecessor is beta-carotene, which splits to form two retinols, (which are vitamin A) which can form retinoic acid (which regulates gene expression in skin development) or 11-cis retinal, which is used for vision

• its derivative 11-cis retinol is used for visual perception and helps rod and cone cells in the retina respond to light

• the derivative Retin-A is used to treat severe acne and wrinkled skin

all vitamins structure

• one ring with a long hydrocarbon chain OR

• two rings with a long hydrocarbon chain in between them

lipid vitamins

A, D, D3, E, K, Q

• cannot be made in the body, so require a proper diet to be obtained

• ADEK are all fat soluble

vitamin A is found in

• fish oils, liver, eggs, whole milk, butter

• people developed rice that expresses beta-carotene so that people do not become vitamin A deficient (since beta-carotene cleaves to form vitamin A)

• deficiency causes dry skin and eyes, delayed development, and night blindness

vitamin D is found in

• milk, butter

• deficiency causes defective bone formation or rickets

vitamin D3 is found in

• when we get UV light from the sun

• regulates metabolism of calcium uptake in the kidneys, intestine, and bone

what is the only difference between Vitamin D and D3 structure?

D3 has one less double bond

vitamin E

• destroys oxygen radicals (which are harmful)

• found in eggs, oil, wheat germ

• is an antioxident

• deficiency causes scaly skin and muscle weakness

vitamin K

• helps blood clot

• deficiency slows blood clotting

• K1 cofactor is found in green plant leaves

Vitamin Q / ubiquinone

• used as e- carrier in the ETC of ATP synthesis in mitochondria and chloroplasts

• aka coenzyme Q

eicosanoids

lipids that act as paracrine hormones/ signaling molecules

• parent compound is arachidonic acid, which is just one chain of a phospholipid, which gets cleaved to form each subcategory of eicosanoids

• includes prostaglandins, thromboxanes, and leokotrienes

• different enzymes modify arachidonic acid to form the three subcategories

arachidonic acid

a chain in a phsopholipid that gets cleaved to form the eicosanoids

prostaglandins

• an eicosanoid that contains a 5 carbon ring

• stimulate smooth muscle, elevates blood, uterine contractions, part of inflammatory response, pain reception

thromboxanes

• an eicosanoid that contains a 6 carbon ring with an ether

• produced by platelets for blood clotting

NSAIDS

Non-Steroidal Anti-Inflammatory Drugs

• treat the inflammatory response by inhibiting COX enzymes, which are what break apart arachidonic acid to form prostaglandins and thromboxanes

leukotrienes

• eicosanoids formed of 3 conjugated double bonds

• trigger smooth muscle contraction in the airway, which can trigger anaphylaxis

• predisone targets the enzyme that breaks down arachidonic acid into leokotriene to reduce the effects of possible anaphylaxis/ airway contraction

know this chart

main role of sphingolipids

cell recognition

• since their sugars are easily detected on the cell surface

cholesterol is the precursor for

steroid hormones

• cholesterol is also a membrane lipid